Little is known about the molecular mechanisms involved in taste sensation; however, there are indications that both sweet and bitter taste detection involve G-protein mediated processes. We have identified and characterized two new G- protein coupled receptors, TR1 and TR2, that are expressed in distinct subsets of taste receptor cells. TR1 and TR2 are specifically localized to the taste-pore region of receptor cells indicating that they mediate primary taste sensation in response to specific ligands. Moreover, the sequence divergence between these two receptors and the marked difference in the regional distribution of their expression in the oral cavity indicate that these receptors probably respond to different ligands and may mediate discrimination of distinct modalities. We are characterizing the functional properties of these receptors to assess their role in taste. The molecular components of olfactory signal transduction in the main olfactory epithelium (MOE) and vomeronasal organ (VNO) are being studied to elucidate mechanisms involved in odor and pheromone sensation. We have identified a family of putative pheromone receptors (V2Rs) that consists of about 100 distinct members (genes) in rodents. The wide variety of receptor sequences indicates that pheromones themselves are likely to be a diverse class of molecules. V2Rs are specifically expressed in small subsets of VNO receptor neurons, suggesting that small groups of receptor cells with distinct activation profiles exist, which provides a model for discrimination of distinct pheromonal components. The expression pattern of V2Rs resembles that of the two other very large gene families of putative chemosensory receptors that are found at high levels in small sub-populations of other sensory neurons in the VNO and MOE. These three families of receptors are likely to be the primary means whereby chemicals are distinguished. They also provide molecular markers for dissecting the mechanisms involved in generating and maintaining the organization of the main and accessory olfactory systems. - Taste, Pheromone, Vomeronasal, Olfactory, G-protein